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Depression has been linked to an increased risk of Alzheimer's, and many have suspected that risk is tied to changes in the brain caused by depression. The theory has been that depression shrinks specific areas, leaving the brain vulnerable to the development of Alzheimer's. However, this study found that's not the case.

"We don't know yet whether depression contributes to the development of Alzheimer's disease or whether another unknown factor causes both depression and dementia," lead researcher Dr. Monique M.B. Breteler, from the Erasmus University Medical Center in Rotterdam, said in a statement. "We'll need to do more studies to understand the relationship between depression and dementia."

In the study, Breteler, and her colleagues collected data on 486 people, aged 60 to 90, who did not have dementia.

Among these individuals, 134 had had at least one episode of depression, according to the report in the April 8 issue of Neurology.

During an average six years of follow-up, 33 people developed Alzheimer's disease. The researchers found that those who had had an episode of depression were 2.5 times more likely to develop Alzheimer's compared with people who had never had depression. For people whose depression occurred before they were 60, the risk for developing Alzheimer's was fourfold greater than people who had never had depression, the researchers reported.

One goal of Breteler's research was to determine if depression causes changes in the brain that increase the risk of Alzheimer's disease, as had been suspected by other scientists.

Researchers have proposed that depression leads to a loss of cells in the areas of the brain called the hippocampus and the amygdala, thereby increasing the risk for Alzheimer's. However, Breteler's group didn't find any difference in the size of those areas of the brain in people with or without depression.

In addition, Breteler's team found that people who had symptoms of depression at the start of the study were no more likely to develop Alzheimer's than those who did not have the symptoms.

Even though the study found a connection between depression and Alzheimer's, experts continue to debate whether such a connection really exists.

"There are quite a few papers about the association between depression and Alzheimer's, with conflicting results," said Yaakov Stern, a professor of clinical neuropsychology at Columbia University in New York City. "No one really knows if there is a connection between depression and Alzheimer's."

"Depression may be a risk factor for developing dementia. I believe that's true," said Dr. Gary Kennedy, director of geriatric psychiatry at Montefiore Medical Center in New York City. "Depression is also one of the side effects of dementia.

"So there is an overlap relationship that makes it very difficult to look at the more interesting question of whether, if we treat depression could we prevent dementia," Kennedy said.

Kennedy noted that studies have shown that depression in older people appears to be an early sign of developing dementia. However, whether that's the beginning of dementia or an independent risk factor for dementia isn't known, he said.

Even though the clinical implications for the association between depression and dementia aren't clear, Kennedy believes that older people with depression should have their depression treated. "There's even more reason to make sure depression is aggressively treated," he said.

Adding to the debate about the relationship between Alzheimer's and depression, a paper in the April issue of the Archives of General Psychiatry also suggests that that depression may be a risk factor for Alzheimer's.

In the study, Robert S. Wilson, of Rush University Medical Center in Chicago, and his colleagues found that among 917 older men and women, those who had symptoms of depression at the beginning of the study were more likely to develop Alzheimer's.

"Understanding the mechanisms linking depressive symptoms with dementia could suggest novel approaches to delaying dementia onset, because animal research suggests diverse means by which the adverse effects of chronic stress may be modified," Wilson's team wrote.

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